Disturbances in the murine hepatic circadian clock in alcohol-induced hepatic steatosis.

Abstract:

:To investigate the role of the circadian clock in the development of alcohol-induced fatty liver disease we examined livers of mice chronically alcohol-fed over 4-weeks that resulted in steatosis. Here we show time-of-day specific changes in expression of clock genes and clock-controlled genes, including those associated with lipid and bile acid regulation. Such changes were not observed following a 1-week alcohol treatment with no hepatic lipid accumulation. Real-time bioluminescence reporting of PERIOD2 protein expression suggests that these changes occur independently of the suprachiasmatic nucleus pacemaker. Further, we find profound time-of-day specific changes to the rhythmic synthesis/accumulation of triglycerides, cholesterol and bile acid, and the NAD/NADH ratio, processes that are under clock control. These results highlight not only that the circadian timekeeping system is disturbed in the alcohol-induced hepatic steatosis state, but also that the effects of alcohol upon the clock itself may actually contribute to the development of hepatic steatosis.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Zhou P,Ross RA,Pywell CM,Liangpunsakul S,Duffield GE

doi

10.1038/srep03725

subject

Has Abstract

pub_date

2014-01-16 00:00:00

pages

3725

issn

2045-2322

pii

srep03725

journal_volume

4

pub_type

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